Tumor response assessment has been a foundation for advances in cancer therapy. Conventionally, oncologists relied on one-dimensional size measurements based on Response Evaluation Criteria in Solid Tumors (RECIST), as a guide to define response and progression, and decide when to switch therapy. However, recent clinical observations have indicated that RECIST alone does not fully characterize response and progression in genomically-characterized patients with specific tumor types, such as melanoma, renal cell carcinoma, and lung cancer treated with targeted therapies. For example, experienced thoracic oncologists continue to treat NSCLC patients harboring EGFR mutation with EGFR-TKI for extended periods of time after progression by RECIST, because their tumors grow slowly suggesting that some tumor cells remain sensitive to erlotinib. There is a critical need for additional radiographic strategies to define response and progression of solid tumor.